DESCRIPTION: (Applicant's Abstract) The goal of the proposal is to understand the nature of addictive behavior. Specifically, the cognitive, motivational, and neurobiological dimensions of that behavior that are dysfunctional. We propose to study human smokers and nonsmokers and non-human subjects to test the hypothesis that the control of conscious control over the decision to engage in a voluntary action is generally one of inhibition and not of initiation. That is, the planning and execution of an action are usually completed prior to the person becoming aware of it. However, it is hypothesized that an agent can still, at some point after the instant of awareness of a decision, "veto" (or inhibit) the decision and thereby cancel the motor command. We further hypothesize that drugs affect the timing between decision making (DM) and awareness (A) and thus the ability to "veto" the action. We will also examine the motivational regulation of the direction of attention and its effect on this temporal window of conscious awareness of a decision to act. Finally, we will examine the hypothesis that the objective, electrophysiological indices of DM-A timing occur in non-human primates and are modulated by motivationally-directed, arousal-related activity in the noradrenergic system. Studies will examine event-related potential (ERPs) components extracted from the ongoing EEG. ERPs are sensitive to the temporal dynamics of system-wide information processing, and analogs of the readiness potential (RP), N100 and P300 components will be sought. These components have been hypothesized to reflect aspects of decision making and attention (i.e., motor, sensory, cognitive, respectively) and can be used as time markers of when an event occurred with respect to awareness of the event. Paradigms based on Benjamin Libet's work (1985), specifically designed to examine DM-A timing will be used, as well as paradigms that induce high incentive and/or anxiety. Animal behavioral paradigms will incorporate systematic variations in stimulus and response contingencies similar to those used in the human studies. Animal ERPs will be analyzed to determine whether they exhibit analogous potentials systematically time-locked to aspects of the behavioral or sensory paradigms. Pharmacological agents will be administered systematically or infused locally at target sites in animals to activate or suppress neuronal noradrenergic activity to determine its necessary and sufficient role in the onset, duration, magnitude, spatial distribution, or functional properties of DM-A timing. The outcome of these studies will identify more "objective" indices of decision making, provide a better understanding of conscious control over actions, determine the sensitivity of this process to motivational stimuli, and clarify the role that the noradrenergic system plays in it. With such an understanding it will be easier to design rational cognitive or pharmacological therapies to ameliorate and prevent drug abuse.